In this proposal we describe experiments to define the functions of eosinophils. In prior studies we have shown 1) that a rabbit antiserum to guinea pig eosinophils (AES) will ablate eosinophils from the blood and peritoneal cavity of the guinea pig, and 2) that guinea pig eosinophils contain a major basic protein (MBP). The major basic protein is remarkable in that it accounts for the bulk of eosinophil granule protein, is very basic containing 13% arginine, and readily polymerizes to disulfide linked polymer. We plan to use AES and MBP as probes to define eosinophil function. First, with AES we will complete ongoing experiments dealing with the role of eosinophils in hypersensitivity reactions. Next, we plan to develop an animal model for chronic ablation of eosinophils using either the guinea pig, rat, or mouse so that the role of the eosinophil in parasitic infections, antibody formation, tumor resistance and fertility can be determined. Second, we plan to continue investigation of the MBP to determine its primary structure, its immunogenicity, its cellular localization and what role it may play in various biological reactions. Specifically, we plan to determine whether MBP can serve as a hydrogen donor in the reaction of eosinophil peroxidase with hydrogen peroxide, whether MBP alters lymphoid cell growth, phagocytosis, parasite infectivity, the release and activity of the mediators of anaphylaxis and finally the formation and reactivity of free radicals in inflammation. BIBLIOGRAPHIC REFERENCES: Gleich, G. J., Loegering, D. A., Mann, K. G. and Maldonado, J. E.: Comparative Properties of the Charcot-Leyden Crystal Protein in the Major Basic Protein from Human Eosinophils. J. Clin. Invest. 57:633-640, 1976. Lewis, D. M., Loegering, D. A. and Gleich, G. J.: Isolation and Partial Characterization of a Major Basic Protein from Rat Eosinophil Granules. Proc. Soc. Exp. Biol. Med. 152:512-515, 1976.